Project description:A secreted factor in bone marrow associated with metastatic gastric cancer was indentified through expression profiling in bone marrow of stage III and stage IV gastric adenocarcinoma. In the study presented here, bone marrow samples from patients with stage III or stage IV gastric adenocarcinoma were used to acquire expression profiles.
Project description:A secreted factor in bone marrow associated with metastatic gastric cancer was indentified through expression profiling in bone marrow of stage III and stage IV gastric adenocarcinoma.
Project description:Gastric cancer is the second most common cause of cancer-related death worldwide. Up to 80% of patients who undergo curative surgical resection develop locoregional or distant recurrence. A recent large-scaled meta-analysis on 3,838 patients from 17 trials has demonstrated survival benefit from adjuvant chemotherapy when compared to surgery alone. Furthermore, INT-0116 study has demonstrated a survival benefit from postoperative chemoradiation therapy with 5-fluorouracil and leucovorin in gastric cancer patients. Despite these advances, 5-year disease-free survival rates remain poor for patients diagnosed with stage III or IV gastric cancer (stage IIIA, 57.6%, stage IIIB, 39.6%; and stage IV 26.3%) underscoring the need for development of new targeted agents. On the other hand those diagnosed with stage Ib/II gastric cancer have moderate 5 year recurrence rate (76.2%) and suggest the presence of significant molecular heterogeneity with varying prognosis. We hypothesized that gene expression of profiling of formalin fixed paraffin embedded tumor (FFPET) samples using whole genome cDNA-mediated Annealing, Selection, Extension, and Ligation (WG-DASL) assay could be used to develop robust prognostic profiles for gastric cancer treated with chemoradiotherapy that are independent of clinicopathological features. We have identified and validated a gene expression signature that predicts recurrence after curative resection. We also performed pathway analyses to delineate aberrant pathways in aggressive gastric cancer which suggest targeted treatment strategies.
Project description:Genome wide DNA methylation profiling of normal and different Alzheimer Braak stages samples. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included 5 controls, 5 Braak stage I-II, 5 Braak stage III-IV and 5 Braak stage V-VI.
Project description:Contain data of 2 studies
1: 82 nodal stage 1 FL cases and 139 stage III/IV cases
2: 44 watch and wait stage III/IV and 46 Immediate treatment stage III/IV
targeted sequencing data of 369 genes and 12 translocation regions
whole genome shallow sequencing data
Project description:<p><strong>OBJECTIVE:</strong> Rheumatoid arthritis (RA) is a progressive disease including four stages, where gut microbiome is associated with pathogenesis. We aimed to investigate stage-specific roles of microbial dysbiosis and metabolic disorders in RA.</p><p><strong>METHODS:</strong> We investigated stage-based profiles of faecal metagenome and plasma metabolome of 76 individuals with RA grouped into four stages (stages I-IV) according to 2010 RA classification criteria, 19 individuals with osteroarthritis and 27 healthy individuals. To verify bacterial invasion of joint synovial fluid, 16S rRNA gene sequencing, bacterial isolation and scanning electron microscopy were conducted on another validation cohort of 271 patients from four RA stages.</p><p><strong>RESULTS:</strong> First, depletion of <em>Bacteroides uniformis</em> and <em>Bacteroides plebeius</em> weakened glycosaminoglycan metabolism (p<0.001), continuously hurting articular cartilage across four stages. Second, elevation of <em>Escherichia coli</em> enhanced arginine succinyltransferase pathway in the stage II and stage III (p<0.001), which was correlated with the increase of the rheumatoid factor (p=1.35 x 10^-3) and could induce bone loss. Third, abnormally high levels of methoxyacetic acid (p=1.28 x 10^-8) and cysteine-S-sulfate (p=4.66 x 10^-12) inhibited osteoblasts in the stage II and enhanced osteoclasts in the stage III, respectively, promoting bone erosion. Fourth, continuous increase of gut permeability may induce gut microbial invasion of the joint synovial fluid in the stage IV.</p><p><strong>CONCLUSIONS:</strong> Clinical microbial intervention should consider the RA stage, where microbial dysbiosis and metabolic disorders present distinct patterns and played stage-specific roles. Our work provides a new insight in understanding gut-joint axis from a perspective of stages, which opens up new avenues for RA prognosis and therapy.</p>
Project description:Gene expression profiles of individual bone marrow cells were acquired by Drop-Seq. Total bone marrow (TBM) and weakly lineage depleted bone marrow (DBM; CD235a and/or Cd45 negative) and stromal cells (STRO-1 positive or collagenase IV released) were analysed.
Project description:Gastric cancer is the second most common cause of cancer-related death worldwide. Up to 80% of patients who undergo curative surgical resection develop locoregional or distant recurrence. A recent large-scaled meta-analysis on 3,838 patients from 17 trials has demonstrated survival benefit from adjuvant chemotherapy when compared to surgery alone. Furthermore, INT-0116 study has demonstrated a survival benefit from postoperative chemoradiation therapy with 5-fluorouracil and leucovorin in gastric cancer patients. Despite these advances, 5-year disease-free survival rates remain poor for patients diagnosed with stage III or IV gastric cancer (stage IIIA, 57.6%, stage IIIB, 39.6%; and stage IV 26.3%) underscoring the need for development of new targeted agents. On the other hand those diagnosed with stage Ib/II gastric cancer have moderate 5 year recurrence rate (76.2%) and suggest the presence of significant molecular heterogeneity with varying prognosis. We hypothesized that gene expression of profiling of formalin fixed paraffin embedded tumor (FFPET) samples using whole genome cDNA-mediated Annealing, Selection, Extension, and Ligation (WG-DASL) assay could be used to develop robust prognostic profiles for gastric cancer treated with chemoradiotherapy that are independent of clinicopathological features. We have identified and validated a gene expression signature that predicts recurrence after curative resection. We also performed pathway analyses to delineate aberrant pathways in aggressive gastric cancer which suggest targeted treatment strategies. RNA was extracted from 2-4 sections of 4-μm thick, FFPET sections. Non-tumor elements were removed by manual microdissection before transfer to the extraction tube guided by hematoxylin and eosin stained slides. The samples with RNA concentrations of <40 ng/μL, A260/A280 ratios <1.5 or A260/230 ratios <1.0 were considered as inadequate samples and were excluded from the analysis.